Analgesic Response to Morphine in Sickle Cell Disease

吗啡在镰状细胞病中的镇痛反应

基本信息

批准号：
8286298
负责人：
ANGELA M ELLISON
金额：
$ 13.15万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8286298
关键词：
Acute Address Adenosine Triphosphate Affect African African American Alleles Analgesics Area Asian Americans Award Binding Candidate Disease Gene Caring Catechols Child Clinical Clinical Pharmacology Code Complex Data Development Dose Drug Exposure Drug Kinetics Drug Prescriptions Drug usage Emergency Medicine Environment Enzymes Ethnic Origin European Event Familiarity Frequencies Gene Frequency Genes Genetic Genetic Polymorphism Genomics Genotype Glucuronosyltransferase Goals Haplotypes Hematology Hispanic Americans Human Individual Instruction Interdisciplinary Study Intervention Intravenous Investigation K-Series Research Career Programs Knowledge Laboratories Lead Measurement Melanocortin 1 Receptor Mentors Mentorship Methyltransferase Morbidity - disease rate Morphine Opioid Opioid Analgesics Opioid Receptor Other Genetics Pain Patients Pattern Pediatric Hospitals Pharmaceutical Preparations Pharmacodynamics Pharmacogenetics Pharmacogenomics Philadelphia Population Race Recurrence Research Research Project Grants Research Training Sampling Scientist Secondary to Sickle Cell Anemia Single Nucleotide Polymorphism Statistical Models Structure Testing Training Uridine Diphosphate Variant abstracting caucasian American clinical epidemiology clinical phenotype design experience genetic risk factor genetic variant genome wide association study improved member novel patient oriented research programs public health relevance response skills symposium vaso-occlusive pain

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of Dr. Angela Ellison, the candidate for this Career Development Award, is to develop interventions that will improve the acute management of vaso-occlusive pain events (VOE) in sickle cell disease (SCD). As part of this award, Dr. Ellison will expand her research training to include skills in the area of pharmacogenomics through mentoring, a structured laboratory experience, completion of relevant coursework, participation in weekly seminars, attendance at national research conferences and completion of the proposed research project. The Children's Hospital of Philadelphia (CHOP) provides an outstanding environment for young-scientists to gain experience, formal instruction, and independence in designing and conducting patient oriented research. Dr. Ellison is receiving mentorship from outstanding clinical and basic scientists with expertise in applied genomics, clinical pharmacology, hematology and emergency medicine. The overall goal of her proposal is to determine the pharmacogenetic factors underlying the inter-individual variation in analgesic response to morphine among patients with SCD. The proposal has four specific aims. The first is to characterize the frequency and pattern of single nucleotide polymorphisms in key candidate genes (OPRM1, COMT, and UGT2B7) among African American subjects with SCD and determine if the identified polymorphisms are associated with ethnicity. The second aim is to develop a clear clinical phenotype of analgesic response in children with SCD. The third aim will determine if morphine administration and the resulting systemic exposure, determined for individual patients by pharmacokinetic measurements, is associated with altered analgesic response to morphine in children with SCD. The relationship between the identified polymorphisms and analgesic response will also be examined. The fourth aim is an exploratory aim to identify other genes which regulate or influence morphine response in children with SCD. We anticipate that these studies will uncover genetic variants that influence morphine sensitivity and that these variants, potentially through specific interactions with other genetic and/or environment factors, will have predictive power in guiding drug and dose selection for the management of VOE in sickle cell disease. PUBLIC HEALTH RELEVANCE: Morphine is the most commonly prescribed drug for treatment of severe vaso-occlusive pain events (VOE) in sickle cell disease (SCD). Variation in analgesic response to morphine is a well known but a poorly understood phenomenon in SCD. The determination of genetic factors which are associated with altered analgesic response to morphine will aid in developing better strategies for the management of acute VOE. (End of Abstract)

描述（由申请人提供）：本次职业发展奖候选人 Angela Ellison 博士的长期目标是开发干预措施，改善镰状细胞病中血管闭塞性疼痛事件 (VOE) 的急性管理。 SCD）。作为该奖项的一部分，埃里森博士将通过指导、结构化实验室经验、完成相关课程、参加每周研讨会、参加国家研究会议和完成拟议的研究，扩大她的研究培训，包括药物基因组学领域的技能。研究项目。费城儿童医院 (CHOP) 为年轻科学家提供了良好的环境，让他们在设计和开展以患者为导向的研究时获得经验、正规指导和独立性。埃里森博士接受了具有应用基因组学、临床药理学、血液学和急诊医学专业知识的杰出临床和基础科学家的指导。她提议的总体目标是确定 SCD 患者对吗啡镇痛反应的个体间差异背后的药物遗传学因素。该提案有四个具体目标。第一个是表征非裔美国 SCD 受试者中关键候选基因（OPRM1、COMT 和 UGT2B7）单核苷酸多态性的频率和模式，并确定所识别的多态性是否与种族相关。第二个目标是开发 SCD 儿童镇痛反应的明确临床表型。第三个目标是确定吗啡给药和由此产生的全身暴露（通过药代动力学测量针对个体患者确定）是否与 SCD 儿童对吗啡镇痛反应的改变有关。还将检查已鉴定的多态性和镇痛反应之间的关系。第四个目标是探索性目标，以确定调节或影响 SCD 儿童吗啡反应的其他基因。我们预计这些研究将揭示影响吗啡敏感性的遗传变异，并且这些变异可能通过与其他遗传和/或环境因素的特定相互作用，在指导镰状细胞病 VOE 治疗的药物和剂量选择方面具有预测能力。公共卫生相关性：吗啡是治疗镰状细胞病 (SCD) 严重血管闭塞性疼痛事件 (VOE) 的最常用处方药物。吗啡镇痛反应的变化是 SCD 中众所周知但人们知之甚少的现象。确定与吗啡镇痛反应改变相关的遗传因素将有助于制定更好的急性 VOE 治疗策略。（摘要完）